Leukocytes have the ability to adhere and migrate in vitro and in vivo in response to various stimuli such as inflammatory mediators. In an attempt to study this process in molecular detail, I have chosen to work with HL-60 promyelocytic leukemia cells which are deficient in cell-substrate adhesive ability in the undifferentiated state. Previous work and my preliminary data indicate that they can be induced to become adhesive and migratory leukocytes when they are treated with phorbol esters alone or with combinations of other chemical agents and phorbol esters. Both the cell-substrate adhesion and migration observed with these treatments can be completely inhibited by a monoclonal antibody derived against the common beta subunit of the leukocyte integrin receptors (LFA-1, MAC-1, 150,95). Current experiments are focusing on the identification of the ligands involved in the adhesive events and on how phorbol esters are dramatically stimulating adhesive and migratory response. Leukocyte proteolytic enzymes are felt to play a role during-the invasion of the endothelial basement membrane in vivo which occurs during inflammatory responses. A 94 kDa gelatinase from phorbol ester treated HL-60 cells has been isolated and characterized. The purified enzyme is latent and can be activated by a variety of agents including organomercurials and by denaturants such as acid, urea and SDS. During activation, an autocatalytic cleavage of peptide bonds occurs resulting in several lower molecular weight species. Amino acid sequences from the N-terminus and cyanogen bromide and tryptic peptide fragments have revealed unique sequences and a highly homologous sequence to other collagenase family enzymes. This data shows that this leukocyte gelatinase is a new member of collagenase family of metalloproteases.